1. Academic Validation
  2. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency

DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency

  • Cell Stem Cell. 2009 Aug 7;5(2):168-77. doi: 10.1016/j.stem.2009.05.019.
Timothy Hoey 1 Wan-Ching Yen Fumiko Axelrod Jesspreet Basi Lucas Donigian Scott Dylla Maureen Fitch-Bruhns Sasha Lazetic In-Kyung Park Aaron Sato Sanjeev Satyal Xinhao Wang Michael F Clarke John Lewicki Austin Gurney
Affiliations

Affiliation

  • 1 OncoMed Pharmaceuticals Inc., Redwood City, CA 94063, USA. timothy.hoey@oncomed.com
Abstract

Previous studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis. We developed selective anti-human and anti-mouse DLL4 Antibodies to dissect the mechanisms involved by analyzing the contributions of selectively targeting DLL4 in the tumor or in the host vasculature and stroma in xenograft models derived from primary human tumors. We found that each antibody inhibited tumor growth and that the combination of the two Antibodies was more effective than either alone. Treatment with anti-human DLL4 inhibited the expression of Notch target genes and reduced proliferation of tumor cells. Furthermore, we found that specifically inhibiting human DLL4 in the tumor, either alone or in combination with the chemotherapeutic agent irinotecan, reduced Cancer stem cell frequency, as shown by flow cytometric and in vivo tumorigenicity studies.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P99261
    抗DLL4单克隆抗体
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